Fasting-mimicking Diet in Patients Undergoing Active Cancer Treatment

Phase II Clinical Study of a Fasting-mimicking Diet in Patients Undergoing Oncologic Treatment

This is a pilot, single arm prospective trial assessing feasibility, safety and effects on patient nutritional status of a 5-day fasting-mimicking diet (FMD) in patients with different cancer types and concomitant anticancer treatment.

Study Overview

• Status: Completed
• Conditions: Cancer; Breast Cancer; Colorectal Cancer
• Intervention / Treatment: Other: Prolon

Detailed Description

It is proposed to conduct a single-arm phase II clinical study of a FMD (Prolon, by L-Nutra) in 60 patients with solid or hematologic tumors who undergo treatment with chemotherapeutic regimens, hormone therapies, other molecularly targeted therapies (including kinase inhibitors), biological drugs (including trastuzumab, pertuzumab, cetuximab and bevacizumab) or inhibitors of immune checkpoints (e.g. Opdivo, Keytruda).

Prolon is a FMD lasting five days. It consist of vegetable soups, broths, bars, olives, crackers, herbal teas, supplements of vitamins and minerals. Day 1 of the FMD supplies ~4600 kJ (11% protein, 46% fat, and 43% carbohydrate), whereas days 2-to-5 provide ~3000 kJ (9% protein, 44% fat, and 47% carbohydrate) per day.

Primary endpoints of the study are the feasibility and safety of monthly cycles of the FMD in patients with solid or hematologic tumors who undergo active treatment. Feasibility is monitored through the compilation of a food diary and is defined as the strict adherence to the diet prescribed in all its days with the possibility of admitting the consumption of only 50% of the planned diet and / or a maximum consumption of 4-5 Kcal / kg body weight of food not provided in only one of the five days of each cycle. Furthermore, the dosage of IGF-1 and of urinary ketone bodies allow to identify further cases of non-adherence to the diet.

FMD-emergent side effects are monitored according to the NCI-CTCAE version 5.0.

Secondary endpoints include:

• patient nutritional status as monitored by weight, handgrip strength, bio-impedance and serum markers (ferritin, transferrin, colinesterase).
• Quality of life (QLQ-C30)
• Clinical responses measured by CT, MRI or by blood chemistry tests, dosing of tumor markers and / or molecular biology tests in the case of prostate tumors or hematologic tumors (e.g. PSA in patients affected by prostate cancer, BCR / Abl mRNA in the case of patients undergoing treatment with kinase inhibitors for CML; CM in the case of patients undergoing treatment for multiple myeloma).
• Long-term efficacy (progression-free survival, overall survival).
• Effect of FMD on HOMA index, PCR, circulating levels of IGF-1 and urinary levels of ketone bodies.
• Effect of FMD on lymphocyte subsets, NK cells and antigen-presenting cells with a role documented in antitumor immunity.

It is foreseen that 60 patients will be enrolled.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • GE
    • Genoa, GE, Italy, 16132
      • Alessio Nencioni

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent
• Age > 18 years
• Patients with solid or hematologic tumors undergoing active treatment, including patients who are preparing to start a new treatment with chemotherapeutic regimens, hormone therapies, other molecularly targeted therapies (including kinase inhibitors), biologics (including trastuzumab) , pertuzumab, cetuximab and bevacizumab) or inhibitors of immune checkpoints (eg Opdivo, Keytruda), ie patients in whom treatment is already underway;
• ECOG performance status 0-1
• Adequate organ function
• BMI >21 kg/m2 (with possibility to also enroll patients with 19<BMI<21 based on the judgement of the treating physician)
• Low nutritional risk according to nutritional risk screening (NRS)

Exclusion criteria:

• Diabetes mellitus;
• Previous therapy with IGF-1 inhibitors;
• Food allergies to the components of the FMD;
• BMI <19 kg/m2;
• bio-impedance phase angle <5.0°;
• medium/high nutritional risk according to NRS;
• Any metabolic disorder that can affect gluconeogenesis or ability to adapt to fasting periods;
• Patients who live alone or are not adequately supported by the family context;
• Treatment in progress with other experimental therapies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prolon - FMD; Patients undergoing active cancer treatment are assigned monthly cycles of the fasting-mimicking diet Prolon	Other: Prolon; Prolon by L-Nutra is a medically-designed dietary kit providing the food to eat for five days. Day 1 of Prolon provides ~4600 kJ (11% protein, 46% fat, and 43% carbohydrate), whereas days 2-to-5 provide ~3000 kJ (9% protein, 44% fat, and 47% carbohydrate) per day.; Other Names: fasting-mimicking diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of prescribed diet consumed and intake of any extra food	Feasibility will be monitored through the compilation of a food diary and is defined as the strict adherence to the diet prescribed in all its days with the possibility to admit the consumption of only 50% of the planned diet and / or a maximum consumption of 4- 5 Kcal / kg of food not expected in only one of the days -2, -1, +1 of each cycle.	6 months
Quantification of FMD-emergent adverse events	The side effects of Prolon (hematologic and non-hematologic) will be classified according to NCI CTCAE 5.0	6 months

Collaborators and Investigators

• Sponsor: University of Genova
• Investigators: Principal Investigator: Alessio Nencioni, MD, University of Genoa

Publications and helpful links

General Publications

• Valdemarin F, Caffa I, Persia A, Cremonini AL, Ferrando L, Tagliafico L, Tagliafico A, Guijarro A, Carbone F, Ministrini S, Bertolotto M, Becherini P, Bonfiglio T, Giannotti C, Khalifa A, Ghanem M, Cea M, Sucameli M, Murialdo R, Barbero V, Gradaschi R, Bruzzone F, Borgarelli C, Lambertini M, Vernieri C, Zoppoli G, Longo VD, Montecucco F, Sukkar SG, Nencioni A. Safety and Feasibility of Fasting-Mimicking Diet and Effects on Nutritional Status and Circulating Metabolic and Inflammatory Factors in Cancer Patients Undergoing Active Treatment. Cancers (Basel). 2021 Aug 9;13(16). pii: 4013. doi: 10.3390/cancers13164013.

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2017
• Primary Completion (Actual): April 15, 2021
• Study Completion (Actual): April 15, 2021

Study Registration Dates

• First Submitted: July 12, 2018
• First Submitted That Met QC Criteria: July 12, 2018
• First Posted (Actual): July 23, 2018

Study Record Updates

• Last Update Posted (Actual): October 20, 2022
• Last Update Submitted That Met QC Criteria: October 19, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: cancer; nutritional status; body composition; fasting; fasting-mimicking diet
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 308CER2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No